NIAID experts and collaborators rapidly initiated scientifically rigorous clinical trials to evaluate the most promising candidate therapeutics for COVID-19. NIAID scientists and NIAID-supported researchers continue to conduct basic, translational and clinical research aimed at identifying effective therapeutics for early COVID-19 infection and for hospitalized patients with more advanced disease.
NIH COVID-19 Treatment Guidelines
NIH formed the COVID-19 Treatment Guidelines in 2020 to provide clinicians with regularly updated guidance on how to care for patients with COVID-19. The COVID-19 Treatment Guidelines Panel critically review and synthesize published data and other authoritative information to develop recommendations. The Panel includes experts in patient management, translational and clinical science, and/or development of treatment guidelines. Read more about the how the Guidelines are developed and see the current NIH COVID-19 Treatment Guidelines.
Adaptive COVID-19 Treatment Trial (ACTT)
In February 2020, NIAID initiated a randomized, controlled clinical trial to evaluate the safety and efficacy of the antiviral remdesivir in hospitalized adults diagnosed with COVID-19. The trial established that remdesivir can reduce time to recovery for hospitalized adults with COVID-19, providing pivotal data for the authorization and approval of the treatment. The trial was designed to be adapted to evaluate additional investigative treatments. The protocol, known as the Adaptive COVID-19 Treatment Trial (ACTT), has been continually modified to evaluate additional therapies in hospitalized adults with COVID-19. The protocol’s second iteration, known as ACTT-2, showed that baricitinib, when given with the antiviral remdesivir, reduced time to recovery for people hospitalized with COVID-19. Please visit NIH’s ACTIV-Associated Trials page for the latest ACTT updates, including ACTT-3 and ACTT-4.
Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)
In April 2020, NIH announced the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership to develop a coordinated research strategy for prioritizing and speeding development of the most promising treatments and vaccines. The effort includes a preclinical working group focused on harmonizing animal model data, expanding access to high throughput screening facilities, comparing approaches to identify assays and creating processes to evaluate viral variant effects on therapeutics and vaccines. ACTIV also includes a therapeutics clinical working group that developed a prioritized list of potential therapeutic candidates for clinical testing and initiated trials evaluating these candidates using scientifically rigorous master protocols.
As part of ACTIV, NIAID is supporting the clinical evaluation of candidate therapeutics in outpatients with COVID-19 as part of the ACTIV-2 protocol as well as in people hospitalized with COVID-19 as part of the ACTIV-3 protocols. NIAID is also supporting the ACTIV-5 “Big Effect Trial” which is assessing whether certain candidate therapeutics show promise against COVID-19 in hospitalized adults and merit advancement into larger clinical trials. Please visit the ACTIV Therapeutics page for the latest updates.
Antiviral Program for Pandemics (APP)
The Antiviral Program for Pandemics aims to develop safe and effective antivirals to combat SARS-CoV-2, the virus that causes COVID-19, as well as to build sustainable platforms for targeted drug discovery and development of a robust pipeline of antivirals against viruses with pandemic potential. Widespread availability of highly effective oral antivirals that can be taken at home early in the course of infection can prevent transmission of the virus and overwhelming surges in hospitalizations, ultimately saving lives. Read more about the Antiviral Program for Pandemics.
Monoclonal Antibodies
Monoclonal antibodies are laboratory-made versions of proteins naturally produced by the immune system. These neutralizing antibodies can bind directly to portions of viruses that attach to and enter cells, preventing them from initiating the infection cycle. Numerous monoclonal antibody therapies have been authorized by the Food and Drug Administration for the treatment of COVID-19.
Scientists at NIAID’s Vaccine Research Center (VRC) collaborated with AbCellera and Lilly to discover monoclonal antibodies for COVID-19, which were developed further by Lilly in partnership with AbCellera. The VRC continues to evaluate various monoclonal antibodies and their ability to neutralize SARS-CoV-2 variants of concern as some variants have shown reduced susceptibility to certain monoclonal antibodies.
NIAID also has led clinical trials of various monoclonal antibodies through the ACTIV-2 and ACTIV-3 protocols as well as through the NIAID-supported COVID-19 Prevention Network.
Read the latest recommendations for using monoclonal antibodies to treat COVID-19 from the NIH COVID-19 Treatment Guidelines Panel.
Host-Directed Strategies and Immunomodulators
Host-directed treatments augment the human body’s defenses against an invading pathogen, such as by impacting inflammation. Some host-directed therapies, including the corticosteroid dexamethasone and the kinase inhibitor baricitinib, are recommended by the NIH Treatment Guidelines Panel for certain people hospitalized with COVID-19.
Results from NIAID’s Adaptive COVID-19 Treatment Trial-2 (ACTT-2) demonstrated that baricitinib, when given with the antiviral remdesivir, reduced time to recovery for people hospitalized with COVID-19. NIAID continues to support basic, translational, and clinical research into host-directed strategies for COVID-19 treatment.
The ACTIV-1 trial, supported by the National Center for Advancing Translational Science (NCATS), is also evaluating promising immune modulator compounds in adults hospitalized with COVID-19.